Clinical pharmacology and therapeutics
-
Clin. Pharmacol. Ther. · Dec 2010
Randomized Controlled Trial Comparative StudyAcute alertness-promoting effects of a novel histamine subtype-3 receptor inverse agonist in healthy sleep-deprived male volunteers.
The alertness-promoting effect of MK-0249 (10 or 50 mg), a histamine subtype-3 receptor (HRH3) inverse agonist (IA), was evaluated in the stimulant reference sleep deprivation model (SRSDM) using a double-blind, double-dummy, placebo- and modafinil- (200 mg) controlled, four-period crossover design in 24 healthy young men. The two primary hypotheses were related to sleep latency (first appearance of one epoch of stage 2, 3, or 4 or REM sleep, as detected using polysomnography (PSG)) at 8:00 AM on day 2. ⋯ Sleep latency was higher when averaged over all MWT time points (P < 0.0001 for modafinil and for both doses of MK-0249). The alertness-promoting effect with the use of MK-0249 in the SRSDM suggests that HRH3 IAs may be effective in disorders involving excessive somnolence.
-
Clin. Pharmacol. Ther. · Dec 2010
ReviewThe clinical utility of precision medicine: properly assessing the value of emerging diagnostic tests.
Assessments of the clinical utility of biomarkers and genomic tests often ignore individual utility and fail to account for downstream changes to the care delivery model. Tests that identify outliers are often undervalued in favor of those that help direct treatment for the "average" patient. By reducing uncertainty, these tests also enable lower-cost providers and even patients to assume increased responsibility for care in more convenient and affordable settings.
-
Clin. Pharmacol. Ther. · Oct 2010
ReviewThe impact of the Orphan Drug Act on the development and advancement of neurological products for rare diseases: a descriptive review.
Many neurological diseases or conditions are rare disorders. The Orphan Drug Act (ODA) of 1983 was promulgated to promote the development of products for such conditions. In this Opinion piece, we discuss how the ODA has affected neurological diseases, note how current and future sponsors (any person(s) or entity (i.e., academic, corporate body, individual, manufacturer) that applies for an official regulatory action) of products for rare neurological diseases can take advantage of ODA incentives, identify areas of success and continuing needs, and review data that can help drive the future development of products for rare neurological conditions.
-
Clin. Pharmacol. Ther. · Sep 2010
Randomized Controlled TrialGrapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren.
In a randomized crossover study, 11 healthy volunteers ingested 200 ml of grapefruit juice or water three times a day for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren. Grapefruit juice reduced aliskiren peak plasma concentration (C(max)) by 81% (range, 42-91%, P < 0.001), area under the plasma aliskiren concentration-time curve (AUC)(0-infinity) by 61% (range, 15-72%, P < 0.001), and elimination half-life (t(1/2)) from 26.1 to 23.6 h (P = 0.020). Therefore, concomitant use of aliskiren and grapefruit juice is best avoided.